Topotecan Induction Feasible for High-Risk Neuroblastoma

No deaths or dose-limiting toxicities with dose-intensive topotecan, cyclophosphamide induction

TUESDAY, Oct. 18 (HealthDay News) -- Addition of dose-intensive topotecan and cyclophosphamide to induction therapy is feasible for patients with newly diagnosed high-risk neuroblastoma (HRNB), according to a study published online Oct. 17 in the Journal of Clinical Oncology.

Julie R. Park, M.D., from Seattle Children's Hospital, and colleagues investigated the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy in 31 patients with newly diagnosed HRNB. Patients received two cycles of topotecan and cyclophosphamide for five days, then four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing was carried out. Peripheral-blood stem cell (PBSC) harvest occurred after two cycles and surgical resection of residual primary tumor after five cycles. Myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume was performed for those patients achieving at least a partial response. Maintenance therapy was administered twice a day for 14 days in six cycles of 28 days.

The investigators found that there were no deaths related to toxicity or dose-limiting toxicities during induction. Mucositis was seen in 9.7 and 30 percent of topotecan and MSKCC cycles, respectively. PBSC collection was performed for 30 patients, with a median of 31.1 × 106 CD34+ cells/kg, all of which were negative for tumor contamination. Twenty-six of the patients achieved targeted topotecan systemic exposure. At the end of induction, one patient had progressive disease and 26 patients had tumor response. Three-year event-free and overall survival were 37.8 and 57.1 percent, respectively, in the overall cohort.

"This pilot induction regimen was well tolerated with expected and reversible toxicities," the authors write.

One of the study authors disclosed a financial relationship with GlaxoSmithKline Beecham, which funded the study and manufactures topotecan.